DOR/ISL for HIV/AIDS

Not currently recruiting at 114 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Doravirine/Islatravir

Disqualifiers: HIV-1 RNA ≥200 copies/mL, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on assessing the safety and tolerability of a treatment called DOR/ISL, a once-daily pill for individuals with HIV-1. It targets those who have already participated in earlier studies involving this treatment. Participants will take the pill daily for up to 240 weeks or until it becomes commercially available. Ideal candidates are those already on DOR/ISL treatment with low viral levels in their blood. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires participants to already be taking the DOR/ISL medication from previous studies, so you will need to continue with this medication. The protocol does not specify if you need to stop other medications.

Is there any evidence suggesting that DOR/ISL is likely to be safe for humans?

Research has shown that DOR/ISL is generally safe for people with HIV-1. Studies have found that this treatment causes only minor changes in weight and body shape and does not significantly affect fasting lipids.

In one study, most participants (82.9%) experienced some side effects, but only a few (25.7%) were linked to the treatment. This indicates that while some side effects occurred, not all were caused by DOR/ISL. Another study found that patients tolerated DOR/ISL well over time, effectively controlling the virus for up to 96 weeks.

These findings suggest that DOR/ISL is generally well-tolerated and safe for most people. However, like any treatment, some individuals might experience side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

DOR/ISL is unique because it combines two active ingredients, doravirine (DOR) and islatravir (ISL), into a single fixed-dose tablet taken once daily. Researchers are excited because this combination could simplify the treatment regimen for people with HIV/AIDS, making it easier for patients to stick to their medication schedule. Unlike many existing treatments that require multiple pills or higher doses, DOR/ISL offers a more convenient option without compromising efficacy. Additionally, islatravir, one of the components, is known for its long-acting properties, which could lead to more stable viral suppression over time.

What evidence suggests that DOR/ISL might be an effective treatment for HIV/AIDS?

Research has shown that DOR/ISL, the treatment under study in this trial, effectively treats HIV-1. In one study, 85.7% of participants taking DOR/ISL experienced a significant drop in virus levels within the first eight days, indicating a rapid reduction in HIV-1. Another study found that DOR/ISL was as effective as a well-known HIV treatment in controlling the virus. Additionally, DOR/ISL had minimal side effects, such as changes in weight and cholesterol levels. Overall, the evidence supports DOR/ISL's effectiveness in managing HIV-1. ^{1 3 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with HIV-1 who were previously treated with DOR/ISL in certain Merck Sharp & Dohme clinical studies. It's not open to those who are heavily treatment-experienced from other trials.

Inclusion Criteria

I am currently in a clinical study for DOR/ISL by MSD.

Exclusion Criteria

My HIV-1 RNA level is 200 copies/mL or higher.

Has confirmatory laboratory findings for cluster of differentiation 4+ (CD4+) T-cell counts or lymphocyte counts in the prior DOR/ISL study that meet criteria for discontinuation of DOR/ISL

Is a HTE participant receiving treatment in MK-8591A-019 or -033

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DOR/ISL (100 mg/0.25 mg) once daily from Day 1 to Week 96

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Open-label extension

Eligible participants may continue on DOR/ISL until Week 240 or until DOR/ISL becomes commercially accessible

Up to 144 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DOR/ISL

Trial Overview The study is testing the safety and how well people tolerate a combination HIV drug called Doravirine/Islatravir (DOR/ISL). There's no specific hypothesis being tested; it's more about ongoing observation of participants' reactions to the drug.

How Is the Trial Designed?

Group I: DOR/ISL Experimental Treatment 1 Intervention

Participants will receive fixed dose combination (FDC) tablet of DOR/ISL (100 mg/0.25 mg) taken once daily (QD) orally from Day 1 to Week 96. After Week 96, eligible participants may continue on DOR/ISL until week 240 or until DOR/ISL becomes commercially accessible, whichever comes first.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Between 1999 and 2003, a study at Toulouse University Hospital reported 613 adverse drug reactions (ADRs) from antiretroviral drugs affecting 428 patients, highlighting the importance of monitoring these effects.

Most reported ADRs (88.6%) were classified as 'non-serious', but 57% of cases required stopping the suspected medication, indicating that while many reactions were mild, a significant portion still necessitated intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Not Available]. Bandrant, M., Bagheri, H., Cuzin, L., et al.[2016]

In a study of 844 adult HIV patients in Mali, 42.3% experienced adverse drug reactions (ADRs) after starting antiretroviral therapy, with neurological issues being the most common (45.9%).

Zidovudine (AZT) and stavudine (d4T) were identified as significant risk factors for anemia and peripheral neuropathy, emphasizing the need for careful monitoring and potential changes in ART regimens to improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiretroviral-induced adverse drug reactions in HIV-infected patients in Mali: a resource-limited setting experience. Oumar, AA., Dakouo, M., Tchibozo, A., et al.[2022]

Citations

1. merck.com merck.com/news/merck-announces-new-data-from-phase-3-trials-evaluating-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-in-adults-with-virologically-suppressed-hiv-1-infecti/

Merck Announces New Data from Phase 3 Trials ... DOR/ISL data presented show minimal changes in weight and body composition and no clinically meaningful effect on fasting lipids and the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41037024/

Efficacy and safety of doravirine/islatravir in heavily ... From Day 1 to 8, a ≥1.0 log10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0% of the placebo group.

3. academic.oup.com academic.oup.com/cid/article/81/2/322/8074956

Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With ... Doravirine/islatravir (100/0.75 mg) was noninferior to bictegravir/emtricitabine/tenofovir alafenamide in suppressing human immunodeficiency virus type 1 (

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04233216

NCT04233216 | Doravirine/Islatravir (DOR/ISL) in Heavily ... This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose ...

5. journals.lww.com journals.lww.com/aidsonline/abstract/9900/efficacy_and_safety_of_doravirine_islatravir_in.792.aspx

Efficacy and safety of doravirine/islatravir in heavily... : AIDS From Day 1 to 8, a ≥1.0 log 10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0% of the placebo group. At Week ...

6. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/islatravir/patient

Islatravir Patient Drug Record | NIH Available safety data showed that islatravir plus ulonivirine had a comparable side effect profile to that of Biktarvy. Three participants discontinued ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377497/

Brief Report: Efficacy and Safety of Oral Islatravir Once ... Treatment regimens containing islatravir and doravirine maintained viral suppression through week 96 and were well tolerated regardless of dose.